Eradicating Malaria: The End Game Relies on Scientific Alliances

Despite decades of research, there is no reliable vaccine for malaria. Dr. Philip Eckhoff lays out the strategies and collaborations required to eradicate this disease and the half a million lives it takes each year.

Philip Eckhoff: Disease eradication is a very difficult challenge. It’s been tried for a number of different diseases but it’s only worked so far for smallpox which was the first human disease eradicated at the end of the 1970s and for rinderpest which is a cattle disease or was a cattle disease before it was eradicated everywhere in the world. Global eradication has been tried before for malaria in the 1950s and 1960s and it didn’t succeed for a number of reasons.

Right now almost half a million people die every year of malaria. And which is an extraordinarily high number and a terrible burden although this number used to be well over a million. So there has been progress in terms of reducing this burden. What one needs to do is different if you’re starting at a very high burden where everyone is getting infected several times a year. And what one has to do when one’s down to the last couple of cases in a given country.

The tactics change. The strategy changes. The tools change. When starting out in terms of reducing the burden the most important thing is reducing transmission and providing access to treatment. So making sure that people have drugs that work is very important. The second thing will be to give out things like bed nets to reduce the rate at which people actually get new infections. Then all of a sudden you can start to look at a country and see that there’s very little malaria in certain parts of it. And most of the malaria is concentrated in a few remaining pockets.

Then building the right surveillance and information systems and logistics to be able to target enhanced efforts at those sections of the country becomes the next important thing. It gets to the point where not everyone even in the highest remaining transmission areas is infected. We have to figure out who is still driving transmission, who is not receiving access to the right tools and making sure that you extend access to everyone who’s driving transmission and everyone who is still vulnerable to the disease.

And then in the end it becomes very interesting. There will be only a small scattering of cases here and there and finding them and responding to them quickly with good case management ends up becoming one of the most important tools in the end game. So understanding where a given country is along this continuum, scaling up the tools and most importantly the information systems and ability to deliver treatment all along that continuum. Fundamental aspects of health systems end up becoming really important from start to finish.

On a problem like malaria eradication, disease eradication in general, getting rid of infectious diseases, it is very fundamentally an interdisciplinary problem. There will be people from the medical side of things. There will be people from health systems and operations. People who know immunology, drug development, vaccine development, mosquito science, entomologists. At the same time there’s also a really good role for people who are good at mathematics, people who are good at software, people who are good at data systems. And the interesting thing is when you have a question that’s really core to your part of the problem and you bounce it off someone from one of these other disciplines often they will come up with a better way of actually framing and looking at your specific question.

Sometimes they might even find a better question that actually gets rid of the main challenge you were trying to deal with. There’s a famous saying that if a problem seems intractable increase the scope of the problem. And that actually becomes really evident in the power of collaboration. If you’re looking at how can we in this one domain of say drug development get rid of malaria. That might be an intractable question but then you bring in the people who are good at vector biology, the people who are good at vaccines, the people who are good at data information systems and computing and the people who are really good at health systems and logistics. And all of a sudden you have a bigger problem but one where you can actually work together and solve this.

 

It requires a lot of learning in terms of how to speak each other’s language and how to listen to each other. And how to actually take the time to build these bridges to other fields and to really see the advantage and the impact of doing this well. It’s not easy. It’s much easier to just sit in a room and talk to other people from your discipline where you all already speak the same academic or research or operational language. But it is very much worth building these bridges and cross linking.

 

Philip Eckhoff is a

Hertz Foundation Fellow

and recipient of the prestigious Hertz Foundation Grant for graduate study in the applications of the physical, biological and engineering sciences. Eckhoff is Principal Investigator of the disease modeling team at Intellectual Ventures. In this video, he explains what is involved in total global eradication of malaria and how interdisciplinary collaboration is the key to out-thinking and out-maneuvering this disease. With the support of the Fannie and John Hertz Foundation, he pursued a PhD in applied and computational mathematics at Princeton University, receiving his degree in doctorate in 2009.


The Hertz Foundation mission is to provide unique financial and fellowship support to the nation's most remarkable PhD students in the hard sciences. Hertz Fellowships are among the most prestigious in the world, and the foundation has invested over $200 million in Hertz Fellows since 1963 (present value) and supported over 1,100 brilliant and creative young scientists, who have gone on to become Nobel laureates, high-ranking military personnel, astronauts, inventors, Silicon Valley leaders, and tenured university professors. For more information, visit hertzfoundation.org.

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Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
Surprising Science
  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

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